Summary:
The DppABCDF dipeptide transport system is a member of the ATP-Binding Cassette (ABC) Superfamily of transporters [Wu95]. Based on sequence similarity, DppA is the substrate-binding component, while DppB and DppC are the membrane components, and DppD and DppF are the ATP-binding components of the ABC transporter. DppABCDF is similar in sequence and subunit composition to the oligopeptide uptake system OppABCDF, suggesting similar subunit functions.

DppA's unbound structure has been resolved by x-ray crystallography to resolutions of 3.2 Å [Dunten93] and 2.0 Å, and shows two domains connected by two 'hinge' segments [Nickitenko95]. The structure of DppA has also been determined with bound glycyl-L-leucine has been determined to a resolution of 3.2 Å [Dunten95]. The structure reveals that the binding site recognizes the peptide backbone allowing for accommodation of various side chains [Dunten95]. There is also a requirement for an unsubstituted α-amino group for transport of a peptide [Gilvarg65].

Loss of DppA or DppBCDF resulted in pro mutants being unable to utilize Pro-Gly as a proline source [Olson91]. Pro-Gly transport was inhibited by His-Glu, suggesting His-Glu is an additional substrate for DppABCDF [Olson91]. Mutations in dpp displayed resistance to the toxic dipeptide Lys-aminoxyAla, the loss of ability to utilize Leu-Trp as a source of its required amino acids [Payne84], resistance to Gly-Val, Leu-Val, and Val-Leu, and reduced uptake of Gly-Gly [De73]. Substrate specificity of DppA was studied in a filter binding assay in which column fractions were monitored for binding activity towards radioactively labeled dipeptides and tripeptides. DppA was observed to mediate the ATP driven uptake of dipeptides and, to a lesser extent, tripeptides from the periplasm [Smith99b]. When an outer membrane heme receptor is expressed in E. coli, the dipeptide ABC transporter is also capable of transporting heme and the heme precursor, δ aminolevulinic acid, from the periplasm into the cytoplasm [Letoffe06]. Binding of heme to purified DppA has been demonstrated [Letoffe06].

DppA accumulates to high levels when grown in minimal media, but levels of DppA are reduced when the medium is supplemented with casamino acids [Olson91]. DppA levels were decreased after 4 hours exposure to zinc stress [Easton06] and in response to glucose limitation [Wick01]. When grown in rich medium, gcvB deletion mutants had high constitutive expression of dppA compared to the parent strain [Urbanowski00]. dppA expression is also repressed by PhoB during phosphate limitation [Smith92].